| Project/Area Number |
08557017
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Human pathology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
WATANABE Teruo Univ.of Tsukuba Basic Med.Sci.Professor, 基礎医学系, 教授 (40037396)
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| Co-Investigator(Kenkyū-buntansha) |
YAGAMI Kenichi Univ.of Tsukuba Exp.Animal Center, Professor, 動物実験センター, 教授 (40166476)
TOMIOKA Kenichi Yamanouchi Pharmac.Comp.Assoc.Head, 創薬研究本部, 副所長
SHIMOKAWA Tatsuro Univ.of Tsukuba Basic Med.Sci.Assis.Prof., 基礎医学系, 助教授 (50170999)
FAN Jianglin Univ.of Tsukuba Basic Med.Sci.Lecture, 基礎医学系, 講師 (60272192)
富岡 健一 山之内製薬, 創薬研究本部・第2創薬研究所, 副所長
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1996: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | Transgenic Animals / Lipoproteins / Hypercholesterolemia / Rabbit / Apoproteins / Gene expression / Cloning / トランスジェニックウサギ / レムナント / 冠状動脈硬化 / 危険因子 / リボ蛋白 / リボ蛋白(a) |
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| Research Abstract |
For the study of atheroslerosis, we have successfully generated transgenic rabbits expressing either human apolipoprotein(a) [Lp(a)] or lipoprotein lipase (LPL) at the end of 1998.
Apo(a) transgenic rabbits :
Totally, 93 pups were obtained after transplantation into foster mothers. 11 rabbits were found to have transgene integrated into their genome. 3 transgenic rabbits soon after birth and 5 transgenic rabbits show no detectable expression of apo(a) in the plasma. 3 transgenic rabbit lines have been established ; A01 line has 1.8mg/dl, A46 line has 3.4 mg/dI, and A47 line has 4.5 mg/dl of apo(a) in the plasma. A10 line has been bred into F1 and F2 and the following results were obtained. Human apo(a) mRNA expression was mainly found in the liver and kidney. Plasma apo(a), in transgenic rabbits showed a similar mobility to human Lp(a) at pre-beta position. In the plasma of transgenic rabbits, unlike the plasma of transgenic mice, about 80% of the apo(a) was covalently associated with rabbit apo-B and was contained in the fractions with density 1.02-1.10 g/ml, indicating the formation of Lp(a). These results suggest that transgenic rabbits expressing human apo(a) exhibit efficient assembly of Lp(a) and can be used as an animal model for the study of human Lp(a). Now, we have started to breed more F1 for the study of atherosclerosis by feeding cholesterol-rich diet.
LPL transgenic rabbits :
Until now, we have produced 3 LPL transgenic rabbits under the control of chicken b-actin promoter and 4 LPL transgenic rabbits under the control of scavenger receptor promoter. Characterization of these transgenic rabbits are currently underway.
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